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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;29:1858.)
© 2009 American Heart Association, Inc.

Integrative Physiology/Experimental Medicine

Dynamic Observation of Mechanically-Injured Mouse Femoral Artery Reveals an Antiinflammatory Effect of Renin Inhibitor

Jun Ino; Chiari Kojima; Mizuko Osaka; Kosaku Nitta; Masayuki Yoshida

From the Life Science and Bioethics Research Center (J.I., C.K., M.O., M.Y.), Tokyo Medical and Dental University; and the Department of Internal Medicine IV (J.I., C.K., K.N.), Tokyo Women’s Medical University, Japan.

Correspondence to Masayuki Yoshida, MD, Life Science and Bioethics Research Center, Tokyo Medical and Dental University, 1-5-45 Yushima Bldg D-9, Bunkyo-ku, Tokyo 113-8519 Japan. E-mail masa.vasc{at}tmd.ac.jp

Objective— The renin-angiotensin-aldosterone system (RAS) plays a central role in atherosclerosis. To investigate the effects of a direct renin inhibitor aliskiren on vascular inflammation, we conducted leukocyte adhesion assays in vivo and in vitro using a novel real-time imaging system.

Methods and Results— Aliskiren (10 mg/kg/d) or PBS was administered to C57BL/6 mice (6–7 weeks of age; Oriental Yeast, Tokyo, Japan) for 2 weeks via an osmotic pump. Blood pressure was not significantly changed in the 2 groups throughout the experimental period. A perivascular cuff injury was then introduced to the femoral artery and real-time intravital microscopic observation was conducted 24 hours after injury. The number of adherent leukocytes was elevated in the injured mice without aliskiren (43.8±9.3/10^–2 mm²), whereas that was significantly reduced in the mice with aliskiren (18.4±4.4, P<0.05). Treatment of human umbilical vein endothelial cells (HUVECs) with aliskiren significantly reduced the adhesion of THP-1 cells to TNF-–activated HUVECs (P<0.05). Interestingly, TNF-–induced renin activity and angiotensin II production in HUVECs were also blunted by aliskiren. Furthermore, exogenous renin and angiotensin II abrogated the aliskiren-mediated reduction of THP-1 cell adhesion to HUVECs.

Conclusions— Our in vivo and in vitro findings indicate a pivotal role for renin inhibition in vascular inflammation independent of blood pressure.

This study indicates a pivotal role for renin inhibition in vascular inflammation independent of blood pressure in vivo and in vitro. Our findings also suggest a novel antiinflammatory role for aliskiren.

Key Words: atherosclerosis • renin-angiotensin-aldosterone system • renin inhibition • endothelium